7-101163294-C-T

Variant names:

• chr7-101163294-C-T
• rs201997904
• NM_003378.4:c.1550G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003378.4(VGF):​c.1550G>A​(p.Arg517Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R517L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VGF NM_003378.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

Genes affected

VGF (HGNC:12684): (VGF nerve growth factor inducible) This gene is specifically expressed in a subpopulation of neuroendocrine cells, and is upregulated by nerve growth factor. The structural organization of this gene is similar to that of the rat gene, and both the translated and the untranslated regions show a high degree of sequence similarity to the rat gene. The encoded secretory protein also shares similarities with the secretogranin/chromogranin family, however, its exact function is not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05170417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGF	NM_003378.4	c.1550G>A	p.Arg517Gln	missense_variant	Exon 2 of 2	ENST00000249330.3	NP_003369.2
VGF	XM_005250561.6	c.1550G>A	p.Arg517Gln	missense_variant	Exon 2 of 2		XP_005250618.1
VGF	XM_011516549.4	c.1550G>A	p.Arg517Gln	missense_variant	Exon 3 of 3		XP_011514851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3	c.1550G>A	p.Arg517Gln	missense_variant	Exon 2 of 2	1	NM_003378.4	ENSP00000249330.2
VGF	ENST00000445482.2	c.1550G>A	p.Arg517Gln	missense_variant	Exon 2 of 2	5		ENSP00000400884.2

Frequencies

GnomAD3 genomes AF: 0.0000105 AC: 1 AN: 95142 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000384

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1039742 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 509018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000105 AC: 1 AN: 95142 Hom.: 0 Cov.: 20 AF XY: 0.0000228 AC XY: 1 AN XY: 43842

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000384

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.55	.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.022
Sift	Benign	0.27	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0010	B;B
Vest4		0.11
MutPred		0.14		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.043
MPC		0.77
ClinPred		0.093	T
GERP RS		3.5
Varity_R		0.060
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201997904; hg19: chr7-100806575;